P2Y2R is a direct target of HIF-1α and mediates secretion-dependent cyst growth of renal cyst-forming epithelial cells

Journal article


Publication Details

Author(s): Kraus A, Grampp S, Goppelt-Strübe M, Schreiber R, Kunzelmann K, Peters DJM, Leipziger J, Schley G, Schoedel J, Eckardt KU, Buchholz B
Journal: Purinergic Signalling
Publication year: 2016
Volume: 12
Journal issue: 4
Pages range: 687-695
ISSN: 1573-9538


Abstract


Polycystic kidney diseases are characterized by numerous renal cysts that continuously enlarge resulting in compression of intact nephrons and tissue hypoxia. Recently, we have shown that hypoxia-inducible factor (HIF)-1? promotes secretion-dependent cyst expansion, presumably by transcriptional regulation of proteins that are involved in calcium-activated chloride secretion. Here, we report that HIF-1? directly activates expression of the purinergic receptor P2Y2R in human primary renal tubular cells. In addition, we found that P2Y2R is highly expressed in cyst-lining cells of human ADPKD kidneys as well as PKD1 orthologous mouse kidneys. Knockdown of P2Y2R in renal collecting duct cells inhibited calcium-dependent chloride secretion in Ussing chamber analyses. In line with these findings, knockdown of P2Y2R retarded cyst expansion in vitro and prevented ATP- and HIF-1?-dependent cyst growth. In conclusion, P2Y2R mediates ATP-dependent cyst growth and is transcriptionally regulated by HIF-1?. These findings provide further mechanistic evidence on how hypoxia promotes cyst growth.



FAU Authors / FAU Editors

Eckardt, Kai-Uwe Prof. Dr. med.
Medizinische Klinik 4 - Nephrologie und Hypertensiologie
Goppelt-Strübe, Margarete apl. Prof. Dr.
Medizinische Klinik 4 - Nephrologie und Hypertensiologie
Kraus, Andre Dr. rer. nat.
Medizinische Klinik 4 - Nephrologie und Hypertensiologie


External institutions with authors

Aarhus University
Leiden University
Universität Regensburg


How to cite

APA:
Kraus, A., Grampp, S., Goppelt-Strübe, M., Schreiber, R., Kunzelmann, K., Peters, D.J.M.,... Buchholz, B. (2016). P2Y2R is a direct target of HIF-1α and mediates secretion-dependent cyst growth of renal cyst-forming epithelial cells. Purinergic Signalling, 12(4), 687-695. https://dx.doi.org/10.1007/s11302-016-9532-5

MLA:
Kraus, Andre, et al. "P2Y2R is a direct target of HIF-1α and mediates secretion-dependent cyst growth of renal cyst-forming epithelial cells." Purinergic Signalling 12.4 (2016): 687-695.

BibTeX: 

Last updated on 2018-06-10 at 02:55